1. Xenohormetic Phytochemicals Inhibit Neovascularization in Microphysiological Models of Vasculogenesis and Tumor Angiogenesis.
- Author
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Kpeli GW, Conrad KM, Bralower W, Byrne CE, Boue SM, Burow ME, and Mondrinos MJ
- Subjects
- Humans, Female, Pterocarpans pharmacology, Angiogenesis Inhibitors pharmacology, Cell Line, Tumor, Glycine max chemistry, Citrus paradisi chemistry, Endothelial Cells drug effects, Endothelial Cells metabolism, Human Umbilical Vein Endothelial Cells drug effects, Angiogenesis, Flavanones pharmacology, Neovascularization, Pathologic drug therapy, Neovascularization, Pathologic metabolism, Neovascularization, Pathologic prevention & control, Phytochemicals pharmacology, Triple Negative Breast Neoplasms drug therapy, Triple Negative Breast Neoplasms pathology, Triple Negative Breast Neoplasms metabolism
- Abstract
Xenohormesis proposes that phytochemicals produced to combat stressors in the host plant exert biochemical effects in animal cells lacking cognate receptors. Xenohormetic phytochemicals such as flavonoids and phytoalexins modulate a range of human cell signaling mechanisms but functional correlations with human pathophysiology are lacking. Here, potent inhibitory effects of grapefruit-derived Naringenin (Nar) and soybean-derived Glyceollins (Gly) in human microphysiological models of bulk tissue vasculogenesis and tumor angiogenesis are reported. Despite this interference of vascular morphogenesis, Nar and Gly are not cytotoxic to endothelial cells and do not prevent cell cycle entry. The anti-vasculogenic effects of Glyceollin are significantly more potent in sex-matched female (XX) models. Nar and Gly do not decrease viability or expression of proangiogenic genes in triple negative breast cancer (TNBC) cell spheroids, suggesting that inhibition of sprouting angiogenesis by Nar and Gly in a MPS model of the (TNBC) microenvironment are mediated via direct effects in endothelial cells. The study supports further research of Naringenin and Glyceollin as health-promoting agents with special attention to mechanisms of action in vascular endothelial cells and the role of biological sex, which can improve the understanding of dietary nutrition and the pharmacology of phytochemical preparations., (© 2024 The Author(s). Advanced Biology published by Wiley‐VCH GmbH.)
- Published
- 2024
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